ArticlePloS one2013
Unraveling regulatory programs for NF-kappaB, p53 and microRNAs in head and neck squamous cell carcinoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- A p53-responsive microRNA-100 released from cardiomyoblasts serves as an early biomarker for acute coronary syndrome.Human cell · 2026Article
- P53 and the Ultraviolet Radiation-Induced Skin Response: Finding the Light in the Darkness of Triggered Carcinogenesis.Cancers · 2024Review
- Integrated modeling framework reveals co-regulation of transcription factors, miRNAs and lncRNAs on cardiac developmental dynamics.Stem cell research & therapy · 2023Article
- Development of an endoplasmic reticulum stress-related signature with potential implications in prognosis and immunotherapy in head and neck squamous cell carcinoma.Diagnostic pathology · 2023Article
- Bile reflux and hypopharyngeal cancer (Review).Oncology reports · 2021Review
- Article
- Six Glycolysis-Related Genes as Prognostic Risk Markers Can Predict the Prognosis of Patients with Head and Neck Squamous Cell Carcinoma.BioMed research international · 2021Article
- The temporal effects of topical NF-Oncotarget · 2020Article
- The Progressive Mutagenic Effects of Acidic Bile Refluxate in Hypopharyngeal Squamous Cell Carcinogenesis: New Insights.Cancers · 2020Article
- Development of an Immunogenomic Landscape-Based Prognostic Index of Head and Neck Squamous Cell Carcinoma.Frontiers in molecular biosciences · 2020Article
- Article
- Integrated Genomic and Functional microRNA Analysis Identifies miR-30-5p as a Tumor Suppressor and Potential Therapeutic Nanomedicine in Head and Neck Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- NF-κB inhibition reverses acidic bile-induced miR-21, miR-155, miR-192, miR-34a, miR-375 and miR-451a deregulations in human hypopharyngeal cells.Journal of cellular and molecular medicine · 2018Article
- In Vivo Short-Term Topical Application of BAY 11-7082 Prevents the Acidic Bile-Induced mRNA and miRNA Oncogenic Phenotypes in Exposed Murine Hypopharyngeal Mucosa.Neoplasia (New York, N.Y.) · 2018Article
- Analysis of Transcription Factor-Related Regulatory Networks Based on Bioinformatics Analysis and Validation in Hepatocellular Carcinoma.BioMed research international · 2018Article
- Aberrant expression of miR-21, miR-376c and miR-145 and their target host genes in Merkel cell polyomavirus-positive non-small cell lung cancer.Oncotarget · 2017Article
- An integrative method to decode regulatory logics in gene transcription.Nature communications · 2017Article
- NF-κB1, c-Rel, and ELK1 inhibit miR-134 expression leading to TAB1 upregulation in paclitaxel-resistant human ovarian cancer.Oncotarget · 2017Article
- miR-21, miR-155, miR-192, and miR-375 Deregulations Related to NF-kappaB Activation in Gastroduodenal Fluid-Induced Early Preneoplastic Lesions of Laryngeal Mucosa In Vivo.Neoplasia (New York, N.Y.) · 2016Article
- Comprehensive Expression Profiling and Functional Network Analysis of p53-Regulated MicroRNAs in HepG2 Cells Treated with Doxorubicin.PloS one · 2016Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
In head and neck squamous cell carcinoma (HNSCC), mutations of p53 usually coexist with aberrant activation of NF-kappaB (NF-κB), other transcription factors and microRNAs, which promote tumor pathogenesis. However, how these factors and microRNAs interact to globally modulate gene expression and mediate oncogenesis is not fully understood. We devised a novel bioinformatics method to uncover interactive relationships between transcription factors or microRNAs and genes. This approach is based on matrix decomposition modeling under the joint constraints of sparseness and regulator-target connectivity, and able to integrate gene expression profiling and binding data of regulators. We employed this method to infer the gene regulatory networks in HNSCC. We found that the majority of the predicted p53 targets overlapped with those for NF-κB, suggesting that the two transcription factors exert a concerted modulation on regulatory programs in tumor cells. We further investigated the interrelationships of p53 and NF-κB with five additional transcription factors, AP1, CEBPB, EGR1, SP1 and STAT3, and microRNAs mir21 and mir34ac. The resulting gene networks indicate that interactions among NF-κB, p53, and the two miRNAs likely regulate progression of HNSCC. We experimentally validated our findings by determining expression of the predicted NF-κB and p53 target genes by siRNA knock down, and by examining p53 binding activity on promoters of predicted target genes in the tumor cell lines. Our results elucidating the cross-regulations among NF-κB, p53, and microRNAs provide insights into the complex regulatory mechanisms underlying HNSCC, and shows an efficient approach to inferring gene regulatory programs in biological complex systems.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.